Fungal diseases or mycoses may be superficial, affecting primarily skin, hair and mucous membrane, or may be deep or systemic, affecting lungs and other internal organs. The superficial mycotic infections which are caused by organisms referred to as dermatophytes are generally considered more annoying than serious. The deep or systemic mycotic infections which are caused generally by different organisms are quite serious, frequently resulting in death.
Antifungal agents considered with specific reference to deep or systemic fungal infections caused by organisms such as Candida species, Cryptococcus neoformans, Histoplasma capsulatum and the like are found for the most part to be fungistatic, i.e., merely inhibit the growth of the fungal organism without effecting a kill. A few fungicidal agents are known. Amphotericin B and other polyenes are known to damage membranes that contain ergosterol and therefore are effectively fungicidal. However, their use is normally precluded because of a number of severe side effects. Other possibly fungicidal drugs, e.g. 5-fluorocytosine, have side effects or may be limited by the scope of their spectrum. 5-Fluorocytosine is further limited by the ease with which an organism develops resistance to it. In the search for antifungal drugs for treating systemic infections, it is desirable to find a drug or a combination of drugs which is effective at low concentration levels thereby minimizing side effects. It is particularly desirable to find a drug or a combination of drugs in which the resultant drug is fungicidal.